Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis

Chronic Kidney Disease Clinical Trial

Official title:

A Randomized, Double-Blinded, Placebo-Controlled, Crossover, Multicenter Phase III Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in Chronic Kidney Disease Patients Receiving Chronic Hemodialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01503021
• Other study ID #: RMTI-SFP-6
• Status: Completed
• Phase: Phase 3
• First received: December 29, 2011
• Last updated: April 21, 2015
• Start date: November 2011
• Est. completion date: January 2014

Study information

• Verified date: April 2015
• Source: Rockwell Medical Technologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the parent study is to assess the short-term safety and tolerability of soluble ferric pyrophosphate (SFP) in dialysate administered to a large number of representative adult chronic kidney disease patients on hemodialysis (CKD-HD).

The purpose of the extension study is to assess the long-term safety and tolerability of SFP.

Description:

Parent Study: randomized, double-blinded, crossover, up to 6 weeks, 700 patients. Patients were randomized to receive SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate or placebo (standard liquid bicarbonate concentrate) x 2 weeks, then a 1 week washout, then crossed over to the alternate treatment x 2 weeks.

Extension Study: open-label, single active arm, uncontrolled study, up to 53 weeks, 300 patients. Following completion of the RMTI-SFP-6 parent study, patients could enter the extension study, where they received SFP 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate for up to 52 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 718
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Parent Study, Double Blinded, Crossover:

Key Inclusion Criteria:

1. Adult = 18 years of age.

2. Has chronic kidney disease (CKD) receiving maintenance hemodialysis (HD) (CKD-HD subjects) and regularly undergoing 2 or more dialysis sessions per week.

3. Stable pre-dialysis Hgb = 9.0 to = 12.5 g/dL.

4. Stable pre-dialysis TSAT = 15% to = 45%.

5. Stable pre-dialysis ferritin = 100 to = 1200 µg/L (1200 ng/mL).

Key Exclusion Criteria:

1. Any previous exposure to SFP.

2. Therapy with intravenous, intramuscular or oral iron at any time between the first/screening visit and the randomization visit, or anticipated requirement for iron supplementation during the study period.

3. Non-tunneled vascular catheter for dialysis.

4. Scheduled for kidney transplant within the next 8 weeks.

5. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to screening, or during screening period prior to randomization.

6. Hospitalization within 1 month prior to screening (except for vascular access surgery).

Extension Study, Open Label, Single Active Arm:

Key Inclusion Criteria:

1. Participated in Parent Study RMTI-SFP-6 and completed the follow-up/early term visit.

2. Hemoglobin =12.0 g/dL at screening.

3. TSAT =45% at screening. (Excursion of TSAT by =10% outside this range permitted only if all other inclusion/exclusion criteria are met).

4. Serum ferritin =1000 µg/L at screening. (Excursion of ferritin by =10% outside this range permitted only if all other inclusion/exclusion criteria are met).

Key Exclusion Criteria:

1. Had a serious adverse event attributable (i.e., probably, possibly, or definitely related) to study drug or had an adverse event attributable to study drug that necessitated premature withdrawal from the double-blind, placebo-controlled crossover phase of the parent study RMTI-SFP-6.

2. Non-tunneled vascular catheter for dialysis.

3. Scheduled for kidney transplant within 12 weeks after entry into extension phase.

4. Active infection requiring systemic antimicrobial or antifungal therapy within 2 weeks prior to dosing.

5. Pregnancy or intention to become pregnant during the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Drug:
• SFP
Dialysis with SFP administered via the liquid bicarbonate concentrate at a concentration of 2 µmoles (110 µg) iron/L of dialysate

Other:
• Placebo
Dialysis with standard liquid bicarbonate concentrate without iron

Locations

Country	Name	City	State
United States	Research Across America	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Rockwell Medical Technologies, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2	Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Yes
Other	Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5	Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Yes
Other	Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2	Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Yes
Other	Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5	Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Yes
Other	Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2	Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study	Yes
Other	Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5	Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.	Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study	Yes
Other	Ferritin	The baseline and end of treatment predialysis ferritin levels were evaluated for the 52-week extension study to determine whether soluble ferric pyrophosphate increases iron stores.	Baseline, up to 53 weeks for Extension Study	Yes
Other	Serum Iron	The baseline and end of treatment predialysis serum iron levels were evaluated for the 52-week extension study to determine the effect of soluble ferric pyrophosphate on serum iron.	Baseline, up to 53 weeks for Extension Study	Yes
Other	Transferrin Saturation	The baseline and end of treatment predialysis transferrin saturation were evaluated for the 52-week extension study to confirm clearance of iron derived from soluble ferric pyrophosphate.	Baseline, up to 53 weeks for Extension Study	Yes
Other	Incidence of Patients Meeting Hy's Law Criteria	The peak alanine aminotransferase and the peak total bilirubin levels were evaluated per patient. Laboratory values for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Patients with alanine aminotransferase more than three times the upper limit of normal and also total bilirubin more than two times the upper limit of normal are counted.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Primary	Incidence of Treatment-emergent Adverse Events	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Primary	Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met the protocol criteria for intradialytic hypotension. Intradialytic hypotension events were only to have been reported as adverse events if they exceeded the individual subject's baseline pattern of intradialytic hypotension.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Primary	Incidence of Related Suspected Hypersensitivity Reactions	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met protocol criteria for suspected hypersensitivity reactions.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Secondary	Incidence of Composite Cardiovascular Events	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for composite cardiovascular events were pre-specified in the statistical analysis plan for the study.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Secondary	Incidence of Hemodialysis Vascular Access Thrombotic Events	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for hemodialysis vascular access thrombotic events were pre-specified in the statistical analysis plan for the study.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Secondary	Incidence of Other Thrombotic Events	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for other thrombotic events were pre-specified in the statistical analysis plan for the study.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Secondary	Incidence of Systemic/Serious Infections	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse events of systemic/serious infections were defined in the statistical analysis plan for the study to include infections for which the subject was administered at least 3 doses of an IV antibiotic, and infections for which the subject was hospitalized.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes
Secondary	Incidence of Serious Adverse Events	Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met seriousness criteria.	Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study	Yes